title: Cilomilast counteracts the effects of cigarette smoke in airway epithelial cells.
abstract: Cigarette smoke extracts (CSE) alter TLR4 expression and activation in bronchial epithelial cells. Cilomilast, a phosphodiesterase-4 inhibitor, inhibits cigarette smoke-induced neutrophilia. This study was aimed to explore whether cilomilast, in a human bronchial epithelial cell line (16-HBE), counteracted CSE effects. In particular, TLR4 expression, IP-10 and IL-8 release, lymphocyte and neutrophil chemotactic activity and ERK and IkBa phosphorylation in CSE and LPS-stimulated 16-HBE were assessed. CSE increased TLR4 expression, reduced IP-10 release and lymphocyte chemotactic activity and increased IL-8 release and neutrophil chemotactic activity. Cilomilast reduced TLR4 expression, IL-8 release and neutrophil chemotactic activity as well as it increased IP-10 release and lymphocyte chemotactic activity. All these cilomilast mediated effects were associated with a reduced ERK1/2 and with an increased IkBa phosphorylation. In conclusion, the present study provides compelling evidences that cilomilast may be considered a possible valid therapeutic option in controlling inflammatory processes present in smokers.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy. pace@ibim.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Carina Gabriela
authors.initials: CG
authors.lastname: Uasuf
authors.forename: Antonino
authors.initials: A
authors.lastname: Giarratano
authors.forename: Stefania
authors.initials: S
authors.lastname: La Grutta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Liotta
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D002460:Cell Line; D054357:Chemokine CXCL10 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D009570:Nitriles / Q000627:therapeutic use*; D058988:Phosphodiesterase 4 Inhibitors / Q000627:therapeutic use; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D003509:Cyclohexanecarboxylic Acids; D016209:Interleukin-8; D009570:Nitriles; D058988:Phosphodiesterase 4 Inhibitors; D012906:Smoke; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C433247:Cilomilast